The
FDA
approved
zanidatamab
(Ziihera)
plus
tislelizumab
(Tevimbra)
and
chemotherapy
as
first-line
treatment
for
unresectable/metastatic
HER2-positive
gastroesophageal
cancer.
The
approval
stipulates
use
in
adults
with
unresectable
locally
advanced
or
metastatic
gastric,
gastroesophageal
junction,
or
esophageal
adenocarcinoma
with
HER2
positivity
confirmed
by
an
FDA-approved
test.
The
approval
allows
use
of
zanidatamab
plus
platinum-containing
chemotherapy
with
or
without
tislelizumab.
At
the
same
time
the
agency
approved
two
diagnostic
tests
to
identify
patients
who
are
candidates
for
zanidatamab,
a
HER2-targeting
bispecific
antibody.
“This
approval
represents
an
important
advancement
in
the
treatment
of
metastatic
HER2-positive
GEA
[gastroesophageal
adenocarcinoma],”
said
Geoffrey
Ku,
MD,
of
Memorial
Sloan
Kettering
Cancer
Center
in
New
York
City,
in
a
statement
from
Jazz
Pharmaceuticals.
“Importantly,
similar
outcomes
were
seen
in
patients
whose
tumors
were
PD-L1
positive
or
PD-L1
negative,
suggesting
that
this
regimen
has
the
potential
to
benefit
a
broad
range
of
patients.”
“It
further
underscores
what
we
have
known
for
more
than
15
years:
HER2
testing
at
the
time
of
diagnosis
for
advanced
or
metastatic
gastroesophageal
adenocarcinoma
is
critical
to
optimally
guide
treatment
selection.”
Support
for
the
approval
came
from
the
randomized
phase
III
HERIZON-GEA-01
trial.
The
primary
results
showed
that
patients
who
received
zanidatamab
plus
chemotherapy,
with
or
without
the
PD-1
inhibitor
tislelizumab,
had
about
a
7-month
improvement
in
overall
survival
(OS;
P=0.0043)
and
more
than
a
4-month
improvement
in
progression-free
survival
(PFS;
P<0.0001)
versus
trastuzumab
plus
chemotherapy.
Results
of
the
trial
were
“truly
remarkable”
and
“truly
practice
changing
…
and
a
landmark
for
the
world
of
upper
GI
[gastrointestinal]
malignancies,”
said
Rachna
Shroff,
MD,
of
the
University
of
Arizona
Cancer
Center
in
Tucson,
during
a
discussion
of
the
study
at
the
American
Society
of
Clinical
Oncology
Gastrointestinal
Cancers
Symposium.
GEA
is
a
“tough
disease”
that
has
a
poor
prognosis.
HER2-positive
disease
accounts
for
about
20%
of
cases.
The
most
common
treatment-related
adverse
event
(AE)
was
diarrhea,
occurring
in
75%
of
zanidatamab-treated
patients
and
48%
of
the
control
group.
Grade
≥3
AEs
occurred
in
72%
of
patients
treated
with
zanidatamab
and
tislelizumab
versus
59-60%
of
patients
in
the
other
two
treatment
groups.
Please
enable
JavaScript
to
view
the